New approaches antimicrobial resistance detection and treatment

These research projects are in competition with 71 other studentship projects available across the GW4 BioMed MRC Doctoral Training Partnership. Up to 19 studentships will be awarded to the best applicants. Find out more information about the DTP including how to apply.

This PhD project will look at new approaches that use engineered proteins as novel detection and treatment methods to tackle the growing treat of microbial resistance to commonly used antibiotics.

You will target beta-lactamase enzymes, which are responsible for resistance to the most commonly used antibiotics, the penicillins. Bacterial resistance to antibiotics is one of the most significant crises in modern healthcare. The most widely utilised class of antibiotics (and therapeutics overall) are the beta-lactams class which includes ampicillin, amoxicillin and methicillin. Thus, their decreased effectiveness is major problem. The main mechanism bacteria use to overcome the action of beta-lactams is the production of beta-lactamases (BL) that breakdown the antibiotic.

The project aims to develop a set of proteins that can bind across a broad set of BLs for the purpose of detection and potential treatment. You will initially focus on engineering a set of proteins called the beta-lactamase inhibitory proteins (BLIPs). You will use BLIPs in two ways: to detect the presence of BLs and to act as a new treatment against BLs action. To detect BLs, the student will take a novel nanotechnology approach in which the BLIPs will be interfaced with sensing nano carbon base materials such as graphene and carbon nanotubes: any binding of BLs by BLIPs will change the characteristics of the nano carbon so generating a useful output signal.

As part of the project, you will use cutting edge synthetic biology approaches to interface proteins with nano carbon materials so as to define and optimise the detection process. This will be achieved by reprogramming the underlying genetic code so that new chemistry not present naturally in biology can be incorporated into a protein, in this case the BLIPs, to define how its interacts with nano carbon. You will also utilise the same synthetic biology approach to use BLIPs as potential combination treatments for bacterial infection. The new chemistry used to interface to nano carbon can also be used to improve the BL inhibition properties of the BLIPs. So, we will also enhance the natural antibacterial properties of BLIP.

You will be involved in a highly interdisciplinary project, learning techniques spanning biology, chemistry and physics. BLIP will be engineered and characterised in the Jones lab to contain a new non-native chemistry to facilitate interfacing with nano carbon and to improve its therapeutic use. This will involve both computational and wet lab work (DNA manipulation, protein chemistry), including biochemical and microbiological analysis of the BLIP variants. In collaboration with Elliott and Russo, you will utilise the new reaction handle in BLIP to interface with nano carbon materials (graphene and CNTs). You will have the chance to study the complexes at the single protein molecule level using state-of-the-art imaging approaches (AFM/STM) of BLIP and BLIP-BL complexes on the carbon surface, and begin electrical measurements to correlate output with the type of BL present.

Supervisors

Dr Dafydd Jones

Dr D. Dafydd Jones

Reader, School of Biosciences

Email:
jonesdd@cardiff.ac.uk
Telephone:
+44 (0)29 2087 4290

Programme information

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